tbuckley/cabot-search huggingface dataset:
P1591: HIGH RISK OF BLOOD STREAM INFECTION OF CRE CARRIERS IN NEUTROPENIC CHILDREN WITH HEMATOLOGICAL DISEASES
Authors: L.-P. Liu, Y. Guo, X.-F. Zhu
Journal: HemaSphere (2022)

Background: Neutropenic children with hematological diseases were associated with higher morbidity of carbapenem-resistant enterobacteriaceae (CRE) blood-stream infection (BSI) or colonization. Aims: We aimed to identify the clinical characteristics and clinical outcome caused by CRE-BSI. Methods: 2465 consecutive neutropenic children were enrolled. Antimicrobial susceptibility of CRE strains were explored and potential factors associated with subsequent CRE-BSI and 30-day survival probability were assessed. Results: CRE-carriers were identified in 59/2465 (2.39%) patients and19/59 (32.2%) developed CRE-BSI, while 12/2406 (0.5%) of non-carriers developed CRE-BSI (P<0.001). The 30-day survival probability was significantly lower in patients with CRE-BSI than non-BSI (73.9% vs. 94.9%, P=0.050). Moreover, 30-day survival probability was also poorer in CRE-carriers versus non-carriers (49.7% vs. 91.7%, P=0.048) among CRE-BSI patients. Tigecycline and amikacin exhibited the satisfactory antimicrobial activity against all isolated strains. Fluoroquinolone sensitivity was lower in E. coli (27.1%) versus satisfactory susceptibility of E. cloacae strains (93.1%). CRE-BSI accompanying intestinal mucosal damage were independent risk factors for 30-day survival probability (both P<0.05), while mucositis was also prone to developed CRE-BSI (P=0.034). Image:Summary/Conclusion: CRE-BSI was regarded as an independent predictor predisposing to high mortality in neutropenic children. Moreover, individualized antimicrobial therapy should be adopted due to the different features of patients with separate CRE strains.
PB2290: SEROPREVALENCE OF HEPATITIS B AND C VIRUSES, HIV-1/2 AND SYPHILIS AMONG BLOOD DONORS IN THE CENTRE REGION OF ALGERIA
Authors: F. talbi, D. djameli
Journal: HemaSphere (2022)

Background: Prevention of blood transfusion-transmitted i infections i includes blood donor i screening i and effective infectious i markers screening for i donated blood. Aims: This study i had two i main objectives: i to determine seroprevalence i of HBV, HCV, HIV and syphilis in i blood i donors of i Boufarik i post transfusion and to study i sociodemographic i factors of blood donors. Methods: A iretrospective study i of consecutivei blood donors’ irecords from January 2008 ito December 2018 wasi conducted. Seroprevalence of hepatitis Bi, hepatitis Ci, humani immunodeficiencyi viruses iand isyphilis were determined in 10.300 wholei blood donationsi collected ini the centre region Algeriani Results: The prevalence of serological markers HIV, HBS, HCV and syphilis is respectively 0%, 24%, 0.67 and 23%. Taking two comparative periods: 2008-2012 (n=4139 donations) and 2013-2017 (n=6161 donations): we note an increase in the number of positive cases for the hepatitis B virus: n=07 (2008- 2012) versus n=18 (2013-2017): RR =.69 (.37-1.30), p=.13 (NS) fig.1. An increase in the number of positive cases for the hepatitis C virus: n=02 (2008-2012) vs n=05 (2013-2017): RR =.89 (.21-3.73), p=.45 (NS) fig.2. A stable number of positive cases for the syphilis virus: n=12 (2008-2012) versus n=12 (2013-2017): RR =1.49 (.66-3.31), p=.16 (NS) fig. 3 Image:Summary/Conclusion: These results show that the prevalence of viral infections is stable over time among blood donors in our region. This is due to the establishment of a quality assurance system, the choice of collection site, the selection of donors and finally the improvement of the quality of screening which has contributed to guaranteeing optimal transfusion safety.
Nanoparticle‐Stabilized Emulsion Bioink for Digital Light Processing Based 3D Bioprinting of Porous Tissue Constructs (Adv. Healthcare Mater. 12/2022)
Authors: Jie Tao, Shunyao Zhu, Nazi Zhou, Yu Wang, Haoyuan Wan, Lin Zhang, Yaping Tang, Yingzi Pan, Yang Yang, Jianxiang Zhang, Rui Liu
Journal: Advanced Healthcare Materials (2022)
Abstract 6281: Preclinical development of a bispecific antibody-trap selectively targeting CD47 and CD24 for cancer immunotherapy
Authors: Wenzhi Tian, Song Li, Dianze Chen, Dandan Liu, Huiqin Guo, Chunmei Yang, Li Zhang, Wei Zhang, Xiaoping Tu, Liang Peng, Gui Zhao, Ruliang Zhang, Fan Zhang
Journal: Cancer Research (2022)

Abstract Limited treatment beneficial rate and market saturation of the first generation of immune checkpoint inhibitors (Such as PD-(L)1 inhibitors) have turned the attention of pharmaceutical industry to the next generation of innate immune checkpoints such as CD47/SIRPα and CD24/Siglec-10. Various cancers of lung, breast, colon, prostate, ovarian, stomach, pancreas, myeloid and lymphoid tissues are known to highly express CD47 and/or CD24, which confer cancer cells means of immune-evasion via induction of “Don’t eat me” signals. Precisely and simultaneously neutralizing CD47 and CD24 signaling on tumors, when coupled with an IgG1 antibody’s potent phagocytosis and cytotoxicity activity, may serve as potent immunotherapy for multiple cancer types. We have developed a humanized CD24 neutralizing antibody which has been revealed to neutralize CD24-Siglec-10 interaction and completely eliminate established colon cancer in syngeneic mouse models via proposed mechanisms of antibody-dependent cell cytotoxicity (ADCC), antibody-dependent cell phagocytosis (ADCP), and subsequent tumor-specific immunity as a result of macrophage activation. Using this mAb as backbone, we developed an CD24 mAb-CD47 trap by conjugating the SIRPα decoy receptor to the N-terminal of the antibody heavy chain. Initial in vitro studies indicated that this mAb-trap has simultaneous two-target binding as well as blocking activities. More promisingly, eight administrations of the mAb-trap at 3mg/kg dose in mice bearing triple-negative breast cancer resulted in a complete tumor growth inhibition. Furthermore, in a Herceptin-resistant xenograft tumor model, the mAb-trap is also efficacious and resulted in over 60% of tumor growth inhibition when administrated at 7.2mg/kg. Taken together, our data show that precise neutralization of CD47 and CD24 signaling on tumors using IgG1 antibody may serve as potent monotherapy for cancers. Citation Format: Wenzhi Tian, Song Li, Dianze Chen, Dandan Liu, Huiqin Guo, Chunmei Yang, Li Zhang, Wei Zhang, Xiaoping Tu, Liang Peng, Gui Zhao, Ruliang Zhang, Fan Zhang. Preclinical development of a bispecific antibody-trap selectively targeting CD47 and CD24 for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6281.
Abstract LB129: Analysis of KRAS wildtype pancreatic ductal adenocarcinoma reveals mutation and expression-based similarities to cholangiocarcinoma
Authors: James Topham, Erica Tsang, Joanna Karasinska, Andrew Metcalfe, Hassan Ali, Steve Kalloger, Veronika Csizmok, Laura Williamson, Emma Titmuss, Hui-Li Wong, Richard Moore, Andrew Mungall, Jonathan Loree, Oliver Bathe, Patricia Tang, Rachel Goodwin, Janessa Laskin, Marco Marra, Steven Jones, David Schaeffer, Daniel Renouf
Journal: Cancer Research (2022)

Abstract Introduction Oncogenic KRAS mutations are absent in 10% of patients with pancreatic ductal adenocarcinoma (PDAC) and may represent a subgroup of PDAC with therapy options beyond standard-of-care chemotherapy. While distinct gene fusions have been implicated in KRAS wildtype (wt) PDAC, other traits unique to KRAS wt PDAC remain unexplored. Methods Patients with treatment-naive metastatic PDAC (n=63) received matched tumor/normal whole-genome and RNA sequencing and clinical follow-up as part of the PanGen trial (NCT02869802). Clinical data and mutation, gene fusion and copy alteration frequency was compared between KRAS wt (n=9) and mutant (n=54) groups. Metastatic colorectal adenocarcinoma and cholangiocarcinoma samples from the POG trial (NCT02155621) were incorporated for sequencing-based comparison. Results KRAS wt tumors showed lower frequency of TP53 SNV/indels (p=0.01) and distinct amplifications affecting chr1q genes NR5A2 (p=9.0e-4), MPC2 (p=0.002) and MCL1 (p=0.02) and chr8q gene SQLE (p=0.02). Oncogenic fusions involving NRG1, FGFR2, NTRK2 or BRAF were unique to KRAS wt tumors (67% of samples; p=1e-6). KRAS wt tumors showed expression patterns indicative of cholangiocytes and, when clustered alongside other tumor types, formed a distinct cluster with cholangiocarcinoma samples. Conclusion These data provide the first identification of distinct chr1q/chr8q amplification events unique to KRAS wt PDAC while highlighting novel and striking molecular similarities to cholangiocarcinoma. Taken together, results of the PanGen trial generate new hypotheses relevant to therapeutic targeting of KRAS wt PDAC and rationale towards incorporating KRAS mutation status as part of routine clinical testing in PDAC. Citation Format: James Topham, Erica Tsang, Joanna Karasinska, Andrew Metcalfe, Hassan Ali, Steve Kalloger, Veronika Csizmok, Laura Williamson, Emma Titmuss, Hui-Li Wong, Richard Moore, Andrew Mungall, Jonathan Loree, Oliver Bathe, Patricia Tang, Rachel Goodwin, Janessa Laskin, Marco Marra, Steven Jones, David Schaeffer, Daniel Renouf. Analysis of KRAS wildtype pancreatic ductal adenocarcinoma reveals mutation and expression-based similarities to cholangiocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB129.
PB2108: PREVALENCE AND CLINICAL IMPLICATIONS OF CYCLIN D1 POSITIVE DIFFUSE LARGE B-CELL LYMPHOMA IN CHINA
Authors: X. Liang, R. Hu, C. Wang, Q. Li, T. Yang, B. Guo, C. Xiao, Y. Liu
Journal: HemaSphere (2022)

Background: Cyclin D1 protein expression in lymphocytes is classically associated with mantle cell lymphoma. It has been ralely reported in patients with diffuse large B-cell leukemia (DLBCL), and studies have been few and generally small, and they were no obvious clinical implications attributable to cyclin D1 expression in China. Aims: To investigate clinical implications attributable to cyclin D1 expression n patients with diffuse large B-cell leukemia (DLBCL) in China. Methods: he authors reviewed 541 patients who were diagnosed with DLBCL treated with R-CHOP (rituximab with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone,R-CHOP) in 3 years. Consortium Program and performed clinical, immunohistochemical, and genetic analyses with a focus on cyclin D1. All patients who were cyclin D1-positive according to immunohistochemistry were also assessed for rearrangements of the cyclin D1 gene (CCND1) using fluorescence in situ hybridization. Clinical and immunohistochemical features were performed to compare patients who had DLBCL with and without cyclin D1 expression. Results: In total, 11 patients (2.0%) who had DLBCL that expressed cyclin D1 and lacked CCND1 gene rearrangements. Patients with cyclin D1-positive DLBCL had a median age of 59.45±3.10 years (ranged 48-80 years). There were 7 males and 4 females. B-symptoms were present in 18.2% of patients. 90.9% patients were regarded as IV stage. The International Prognostic Index was high-intermediate and high (>3) in 81.8% of patients. Two or more extranodal sites were involved in 36.4% of patients. CD20 was positive in all cases. These cases showed a strong nuclear positivity for cyclin D1 in the DLBCL, but no expression of CD5 and SOX11 was detected. All cases were consistently negative for CD10, BCL6 was positive in 8 of 11 cases (72.2%), and MUM1 was positive in 9/11 cases (81.8%). The majority of cases (90.9%) showed expression of MYC. All cases showed a proliferation rate above 80%. Patients with cyclin D1-positive DLBCL patients had more Ki-67 proliferation, elevated serum lactate dehydrogenase and more advanced stage (P<.05). The other clinical characteristics, such as sex, age, extraodal site, IPI score, and β macroglobulin level did not differ significantly (P>.05). However, patients with cyclin D1-positive DLBCL had shorter PFS and OS than cyclin D1-negative patients (P<0.05). Cyclin D1-positive DLBCL patients with MYC or MYC/BCL2 coexpression showed poorer prognosis than double protein lymphoma (DPL) patients, but did not significantly (P>.05). Summary/Conclusion: Compared with patients who had cyclin D1-negative DLBCL, cyclin D1-positive DLBCL patients had later staging and greater tumor load with more Ki-67 proliferation. There were no other significant differences in clinical presentation, pathologic features. Cyclin D1-positive DLBCL patients showed poorer overall survival and progression-free survival than cyclin D1-negative patients.
Abstract LB128: Oncolytic HSV-P10 and effects on metabolism as potential therapy for treatment of glioblastoma
Authors: Matthew P. Mullarkey, Upasana Sahu, Bangxing Hong, Balveen Kaur
Journal: Cancer Research (2022)

Abstract Glioblastoma is an aggressive tumor of the central nervous system associated with a very poor prognosis even with surgery and chemoradiation. We have previously developed an oHSV that encodes for PTENα (HSV-P10) and stimulates anti-tumor immunity. This virus is currently licensed by and is being developed by Mesoblast to evaluate safety and efficacy in patients. To understand the effect of PTENα on tumor cell responses to oHSV therapy we performed RNA sequencing of primary GBM cells infected with control or oHSV-P10. We identified a dysregulation of glycolysis in cells infected with oHSV-P10 relative to control oHSV. Since cancer cells rely heavily on glycolysis for energy production (Warburg effect) the impact of PTENα on metabolic switch was significant. RNA sequencing PCR and western blot analysis showed a significant reduction in cellular Hexokinase II expression and downregulation of HIF-1α in HSV-P10 infected cells. Consistent with the function of HIF1 and hexokinase in driving glycolysis we also observed a significant reduction in glucose uptake and lactate release: implying a reduction in glycolysis in cells after being treated with oHSV-P10. Thus, cellular energetics of HSV-P10 infected cells was directed away from glycolysis relative to HSVQ infected cells. Consistent with this we observed increased, oxidative phosphorylation, production of reactive oxidative species and ATP production. Many cancers, including Glioblastoma are known to utilize the glutamine as a substrate for energy production through its entry into the TCA cycle. Blocking this shows a significant decrease in cell viability and ATP production when combined with HSV-P10. These results indicate that combination of HSV-P10 with radiation has a significant therapeutic potential and should be tested in patients for safety and efficacy. Citation Format: Matthew P. Mullarkey, Upasana Sahu, Bangxing Hong, Balveen Kaur. Oncolytic HSV-P10 and effects on metabolism as potential therapy for treatment of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB128.
PB2222: THE PROTECTIVE EFFECT OF THE SPLEEN IN SICKLE CELL PATIENTS. A COMPARATIVE STUDY BETWEEN PATIENTS WITH ASPLENIA AND HYPERSPLENISM.
Authors: S. Peretz, L. Livshits, E. Pretorius, A. Makhro, A. Bogdanova, M. Gassmann, A. Koren, C. Levin
Journal: HemaSphere (2022)

Background: Sickle cell disease (SCD) is caused by a point mutation in the beta globin gene. SCD is characterized by chronic hemolytic anemia, vaso-occlusive events leading to tissue ischemia and progressive organ failure. A chronic inflammatory state is part of the pathophysiology of SCD. Patients with SCD have extremely variable phenotypes, from a mild disease to severe complications including early age death. The spleen is commonly injured in SCD. Early splenic dysfunction and progressive spleen atrophy are common. Splenomegaly and hypersplenism, can also occur with loss of the crucial splenic function. Acute, life-threatening spleen-related complications in SCD are well studied. The implications of the spleen status including asplenia and splenomegaly/ hypersplenism in vaso- occlusive crisis and long-term complications in SCD remain to be determined. Aims: In this study, we compared blood parameters and RBC properties of SCD patients and compared the results between patients with asplenia, to patients with splenomegaly/hypersplenism. In addition, we implemented novel, non-routinely used methods for the evaluation of the functional status of the spleen in those patients. Methods: We evaluated the association between the spleen status with clinical and laboratory parameters in 31 SCD patients divided into two groups: Group a) Patients with asplenia (N=22) (including auto-splenectomy and patients that were splenectomized) vs. Group b) patients with Splenomegaly and or Hypersplenism (N=9). Laboratory studies included: CBC, reticulocyte count, iron metabolism parameters, CRP, Hb variant distribution and D-dimer. Metabolic and morphological red blood cell (RBC) studies included: density gradient (by Percoll), glucose consumption, lactate release and K+ leakage; fetal RBC (F-Cells) and F Reticulocytes, annexin V+, CD71+, oxidative stress measured by GSH presence in RBC and finally HJB count were all analyzed by FC. SEM analysis of RBC was also performed. Results: Patients in group (a) showed significantly higher WBC, platelet, HCT, hemoglobin S, CRP, D-dimer, GGT, cholesterol and transferrin levels than patients in group (b). The percent of hyperchromic RBCs, F-Reticulocytes were lower in patients with asplenia. Important differences were also found between the groups in the studied RBCs metabolic parameters. Summary/Conclusion: Further studies are required to elucidate the effect of the spleen including hyper and hypo-splenia in vaso-occlusive crisis, vascular pathology, and long-term complications of SCD. The benefits and risks of splenectomy compared to chronic transfusion need to be evaluated in clinical trials and the standard approach to manage hypersplenism in SCD patients should be re-evaluated.
Anemia Among Pregnant Women Participating in the Special Supplemental Nutrition Program for Women, Infants, and Children — United States, 2008–2018
Authors: Florence A. Kanu, Heather C. Hamner, Kelley S. Scanlon, Andrea J. Sharma
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Among pregnant women, anemia, a condition of low hemoglobin concentration, can increase risk for maternal and fetal morbidity and mortality, including premature delivery, and other adverse outcomes (1). Iron deficiency is a common cause of anemia, and during pregnancy, iron requirements increase (2). Surveillance of anemia during pregnancy in the United States is limited. The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) Participant and Program Characteristics (PC) data provide an opportunity to establish national and WIC state agency-level* anemia surveillance for WIC participants. National and state agency anemia prevalences among pregnant WIC participants at enrollment were examined using 2008-2018 WIC-PC data. Across all 90 WIC agencies (50 states, the District of Columbia [DC], five territories, and 34 Indian Tribal Organizations), anemia prevalence among pregnant WIC participants at enrollment increased significantly, from 10.1% in 2008 to 11.4% in 2018 (13% increase). Anemia prevalence increased significantly in 36 (64%) of the 56 agencies in states, DC, and territories, and decreased significantly in 11 (20%). Prevalence of anemia overall and by pregnancy trimester were higher among non-Hispanic Black or African American (Black) women than among other racial or ethnic groups. Anemia prevalence was higher among women assessed during the third trimester of pregnancy than among those assessed during first or second trimesters. Routine anemia surveillance using WIC enrollment anemia data can identify groups at higher risk for iron deficiency. Findings from this report indicate that anemia continues to be a problem among low-income women and reinforces the importance of efforts that ensure these women have access to healthier, iron-rich foods before and during pregnancy. This includes ensuring that eligible women are enrolled in WIC early during pregnancy.
P1745: ADHERENCE TO TREATMENT OF HEMATOLOGICAL MALIGNANCIES PATIENTS WITH ANXIETY AND DEPRESSION
Authors: D. E. Vybornykh, T. Moiseeva, E. Gemdzhian, T. Gaponova, D. Novikova
Journal: HemaSphere (2022)

Background: The issue of factors influencing adherence to treatment of patients with hematological malignancies (HM) has not been sufficiently studied. Aims: To establish the features of the influence of anxiety and depressive disorders on treatment adherence, as well as to clarify the factors associated with it in HM patients. Methods: The study included 117 patients: 51 men and 66 women, aged 19 to 67 years, with Hodgkin’s lymphoma (HL) - 88, acute lymphoblastic leukemia (ALL) - 16 and aplastic anemia (AA) - 13 patients. Patients were examined by psychiatrist using the Brief Psychiatric Rating Scale, as well as some psychometric methods. Results: Anxiety and depressive spectrum disorders were detected in 36 (40.9%) patients with HL and 8 (50%) with ALL, in the AA group there were three (23.1%) of such patients. It was found that the average adherence to treatment was in 2/3 of patients, low and high - in the remaining 1/3 of patients. The adherence to treatment it is significantly higher in patients older than 45 years. Signs of depression that negatively correlated with adherence to treatment, were pessimism (Fig.1) and disruption of social ties (Fig.2). Adherence to treatment significantly positively correlates with the following types of attitudes towards the disease: anosognosic, hypochondriac and egocentric, and significantly negatively correlates with the following types of attitudes towards the disease: anxious, melancholic and dysphoric. With medium and low adherence to treatment, the risk of adverse events increases by an average of 1.7 times (Fig.3). Image:Summary/Conclusion: Anxiety/depressive disorders contribute to reduced adherence of HM patients to treatment. Their correction and increased adherence should be carried out jointly by hematologists and mental health professionals.